Occult Metastases Not Alarming in Breast Cancer

Action Points

Note that the presence of micrometastases was associated with poorer outcomes in this study.

Point out, however, that the difference, although statistically significant, was not sufficiently large to justify routine analysis of lymph nodes.

Occult metastases in clinically node-negative breast cancer have a statistically but not clinically significant effect on outcomes, data from a large multicenter clinical trial showed.

Women with micrometastases had a 1.2% decrease in five-year survival compared with patients who were free of micrometastases. Micrometastases were associated with lower overall survival (P=0.03) and disease-free survival (P=0.02) and a shorter distant disease-free interval (P=0.04), according to an article published online in the New England Journal of Medicine.

"Occult metastases were an independent prognostic variable in patients with sentinel nodes that were negative on initial examination," Donald L. Weaver, MD, of the University of Vermont in Burlington, and co-authors wrote in conclusion. "However, the magnitude of the difference in outcome at five years was small.

"These data do not indicate a clinical benefit of additional evaluation, including immunohistochemical analysis, of initially negative sentinel nodes in patients with breast cancer."

The findings came from a new analysis of data from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-32 trial, which compared sentinel-node biopsy and complete axillary dissection with respect to overall survival and disease control.

Results of NSABP B-32 showed that sentinel lymph nodes, as compared with nonsentinel nodes, were more than four times as likely to contain overt metastases and 12 times as likely to harbor occult metastases (Cancer 2000; 88: 1099-1107). Weaver and co-authors reported findings from their examination of the clinical significance of occult metastases in selected axillary lymph nodes.

Investigators sectioned sentinel nodes at 2-mm intervals, embedded the slices in paraffin tissue blocks and examined one routinely stained slide from each block. Evidence of metastases could be confirmed or refuted with immunohistochemical (IHC) staining, but the protocol prohibited routine IHC staining or analysis of deeper tissue levels.

Tissue blocks from negative nodes were sent to a central laboratory for evaluation of additional sections that were 0.5 to 1.0 mm deeper in the block relative to the original surface. The deeper analysis included routine use of hematoxylin and eosin (H&E) testing and IHC staining.

The deeper analysis of sentinel lymph node blocks involved 3,887 patients who agreed to participate in the planned pathologic substudy. The analysis revealed occult metastases in 15.9%. Isolated tumor cells (≤0.2 mm) accounted for most of the metastases (11.1%), followed by micrometastases (>0.2 to ≤2.0 mm, 4.4%), and macrometastases (>2.0 mm, 0.4%).

The presence of occult metastases was associated with adjusted hazard ratios of 1.40 for death (P=0.02), 1.31 for any outcome event (P=0.009), and 1.30 for distant disease (P=0.03). Analysis by the size of the occult metastasis led to similar results.

The five-year survival estimates for patients with occult metastases were 94.6% for overall survival, 86.4% for disease-free survival (DFS), and 89.7% for distant DFS. The same estimates for patients without occult metastases were 95.8%, 89.2%, and 92.5%.

"Occult metastases were not discriminatory predictors of cancer recurrence," the authors wrote in the discussion of their findings. "A total of 138 of 3,884 patients (3.6%) had regional or distant recurrences as first events, and only 30 of these events (21.7%, 0.8% of all patients) occurred in patients with occult metastases."

"Identification of occult metastases does not appear to be clinically useful for patients with newly diagnosed disease in whom systemic therapy can be recommended on the basis of the characteristics of the primary tumor," they added.